Ebola virus disease (EVD) often leads to severe and fatal outcomes in humans with early supportive care increasing the chances of survival. Profiling the human plasma lipidome provides insight into critical illness as well as diseased states, as lipids have essential roles as membrane structural components, signaling molecules, and energy sources. Here we show that the plasma lipidomes of EVD survivors and fatalities from Sierra Leone, infected during the 2014-2016 Ebola virus outbreak, were profoundly altered. Focusing on how lipids are associated in human plasma, while factoring in the state of critical illness, we found that lipidome changes were related to EVD outcome and could identify states of disease and recovery. Specific changes in the lipidome suggested contributions from extracellular vesicles, viremia, liver dysfunction, apoptosis, autophagy, and general critical illness, and we identified possible targets for therapies enhancing EVD survival.

The pathogenesis of human Ebola virus disease (EVD) is complex. EVD is characterized by high levels of virus replication and dissemination, dysregulated immune responses, extensive virus- and host-mediated tissue damage, and disordered coagulation. To clarify how host responses contribute to EVD pathophysiology, we performed multi-platform \&$\#$39;omics analysis of peripheral blood mononuclear cells and plasma from EVD patients. Our results indicate that EVD molecular signatures overlap with those of sepsis, imply that pancreatic enzymes contribute to tissue damage in fatal EVD, and suggest that Ebola virus infection may induce aberrant neutrophils whose activity could explain hallmarks of fatal EVD. Moreover, integrated biomarker prediction identified putative biomarkers from different data platforms that differentiated survivors and fatalities early after infection. This work reveals insight into EVD pathogenesis, suggests an effective approach for biomarker identification, and provides an important community resource for further analysis of human EVD severity.